Development of an improved Scientific Registry of Transplant Recipients deceased donor heart yield model using donor critical care data from the Donor Management Goal Registry cohort.

Organ procurement organizations (OPOs) face increasing regulatory scrutiny, and the performance of predictive models used to assess OPO performance is critical. We sought to determine whether adding deceased donor physiological and critical care data to the existing Scientific Registry of Transplant Recipients (SRTR) heart yield model would improve the model's performance. Donor data and heart transplanted (yes/no), the outcome of interest, were obtained from the United Network for Organ Sharing Donor Management Goal (DMG) Registry for 19 141 donors after brain death, from 25 OPOs. The data were split into training and testing portions. Multivariable LASSO regression was used to develop a statistical model incorporating DMG data elements with the existing components of the SRTR model. The DMG + SRTR and SRTR models were applied to the test data to compare the predictive performance of the models. The sensitivity (84%-86%) and specificity (84%-86%) were higher for the DMG + SRTR model compared to the SRTR model (71%-75% and 76%-77%, respectively). For the DMG + SRTR model, the C-statistic was 0.92 to 0.93 compared to 0.80 to 0.81 for the SRTR model. DMG data elements improve the predictive performance of the heart yield model. The addition of DMG data elements to the Organ Procurement and Transplantation Network data collection requirements should be considered.

Linking nursing outcomes classification to the self- and family management framework.

AIM: Establish linkages between components of the Self- and Family Management Framework and outcomes of the Nursing Outcomes Classification to evaluate the comprehensiveness of outcomes addressing self- and family management in the Nursing Outcomes Classification. DESIGN: Descriptive study. METHODS: Experts conducted a six-step process to establish linkages: (1) preliminary mapping of all relevant nursing outcomes to the framework; (2) development of checklists for team members serving as 'identifiers' and 'reviewers'; (3) mapping all relevant nursing outcomes to the framework; (4) final agreement on mapped outcomes; (5) establishment of inter-rater reliability; and (6) discussion of findings with authors of the Self- and Family Management Framework. RESULTS: Three hundred and sixty-three nursing outcomes were identified as related to the management of chronic disease across all components of the framework: outcomes related to patient self-management (n = 336), family functioning (n = 16) and family caregivers (n = 11). CONCLUSION: The Nursing Outcomes Classification outcomes comprehensively address self-management, and, less so, family functioning, and caregivers. IMPLICATIONS: Established linkages can be used by nurses to track and support patient and family management outcomes across the care continuum. PATIENT OR PUBLIC CONTRIBUTION: Linking standardized nursing outcomes to the Self- and Family Management Framework can assist in goal setting and measurement of nursing care during chronic disease management. This work can help describe to funders, policy makers and others invested in health care reform the specific contributions of nurses to self- and family management of chronic disease. IMPACT: This paper demonstrates the linkages between components of the Self- and Family Management Framework and Nursing Outcomes Classification outcomes. The results of this study offer the opportunity to quantify the impact of nursing care and enhance nursing practice for patients with chronic conditions as well as contribute to developing Nursing Outcomes Classification outcomes that consider self-management processes.

Critical care and ventilatory management of deceased organ donors impact lung use and recipient graft survival.

Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ≥7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ≤8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2 O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.

Pain Management in Clinical Practice Research Using Electronic Health Records.

BACKGROUND: The use of electronic health record (EHR) systems encourages and facilitates the use of data for the development and surveillance of quality indicators, including pain management. AIM: to conduct an integrative review on pain management research using data extracted from EHR in order to synthesize and analyze the following elements: pain management (assessments, interventions, and outcomes) and study results with potential clinical implications, data source, clinical sample characteristics, and method description. DESIGN: An integrative review of the literature was undertaken to identify exemplars of scientific research studies that explore pain management using data from EHR, using Cooper's framework. RESULTS: Our search of 1,061 records from PubMed, Scopus, and Cinahl was narrowed down to 28 eligible articles to be analyzed. CONCLUSION: Results of this integrative review will make a critical contribution, assisting others in developing research proposals and sound research methods, as well as providing an overview of such studies over the past 10 years. Through this review it is therefore possible to guide new research on clinical pain management using EHR.

Salt-sensitive transcriptome of isolated kidney distal tubule cells.

In the distal kidney tubule, the steroid hormone aldosterone regulates sodium reabsorption via the epithelial sodium channel (ENaC). Most studies seeking to identify ENaC-regulating aldosterone-induced proteins have used transcriptional profiling of cultured cells. To identify salt-sensitive transcripts in an in vivo model, we used low-NaCl or high-NaCl diet to stimulate or suppress endogenous aldosterone, in combination with magnetic- and fluorescence-activated cell sorting to isolate distal tubule cells from mouse kidney for transcriptional profiling. Of the differentially expressed transcripts, 162 were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, and 161 were more abundant in distal tubule cells isolated from mice fed high-NaCl diet. Enrichment analysis of Gene Ontology biological process terms identified multiple statistically overrepresented pathways among the differentially expressed transcripts that were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, including ion transmembrane transport, regulation of growth, and negative regulation of apoptosis. Analysis of Gene Ontology molecular function terms identified differentially expressed transcription factors, transmembrane transporters, kinases, and G protein-coupled receptors. Finally, comparison with a recently published study of gene expression changes in distal tubule cells in response to administration of aldosterone identified 18 differentially expressed genes in common between the two experiments. When expression of these genes was measured in cortical collecting ducts microdissected from mice fed low-NaCl or high-NaCl diet, eight were differentially expressed. These genes are likely to be regulated directly by aldosterone and may provide insight into aldosterone signaling to ENaC in the distal tubule.

Healing of canine skin incisions made with monopolar electrosurgery versus scalpel blade.

OBJECTIVE: To determine the influence of monopolar electrosurgery in cutting mode set at 10, 20, or 30 W on surgery time, hemostasis, and healing of cutaneous wounds compared to scalpel incisions. STUDY DESIGN: Randomized blinded control trial. ANIMALS: Dogs (n = 15). METHODS: Four skin incisions were created on either side of the dorsal midline with a scalpel, or monopolar electrosurgery at 10, 20, and 30 W. Surgical time and incisional bleeding were measured. Each incision was assessed daily for edema, erythema and discharge, and complications. Healing was evaluated via histology at 7 days. Results were analyzed for significance at P ≤ .05. RESULTS: Surgical time and hemostasis were improved in all electrosurgery groups. Erythema was reduced in all electrosurgical incisions for days 1-4, but was greater in wounds created via electrosurgery at 20 W than those made with a scalpel blade by day 7. No difference was noted in the degree of edema or presence of wound discharge. All histologic variables of tissue healing were lower in electrosurgical incisions than scalpel incisions (P < .001). Ten incisional complications occurred, all associated with electrosurgery. CONCLUSIONS: The use of monopolar electrosurgery at 10, 20, and 30 W in a cutting waveform improved hemostasis and surgical time when incising canine skin, but delayed healing and increased complications within the first 7 days compared to scalpel incisions.

Minimally Invasive Beaded Electrosurgical Dissectors, Basic Science, and Pilot Studies.

Background: Minimally invasive beaded electrosurgical dissectors ("BEED devices") provide simultaneous sharp dissection, blunt dissection, and electrosurgical coagulation while performing 100 cm2 porcine tissue plane dissections in 0.8 to 3 min with minimal bleeding and no perforations. Objectives: The aim of the study was to report the basic science and potential clinical applications and to video document the speed and quality of planar dissections in in vivo and ex vivo porcine models with thermal damage quantified by thermal and histopathologic measurements. Additionally, in vivo porcine specimens were followed for 90 days to show whether adverse events occurred on a gross or macroscopic basis, as evidenced by photography, videography, physical examination, and dual ultrasonography. Methods: Ex vivo porcine models were subjected to 20, 30, and 50 W in single-stroke passages with BEED dissectors (granted FDA 510(k) clearance (K233002)) with multichannel thermocouple, 3 s delay recordation combined with matching hematoxylin and eosin (H&E) histopathology. In vivo porcine models were subjected to eight 10 × 10 cm dissections in each of 2 subjects at 20, 30, and 50 W and evaluated periodically until 90 days, wherein histopathology for H&E, collagen, and elastin was taken plus standard and Doppler ultrasounds prior to euthanasia. Results: Five to 8 mm width dissectors were passed at 1 to 2 cm/s in ex vivo models (1-10 cm/s in vivo models) with an average temperature rise of 5°C at 50 W. Clinically evidenced seromas occurred in the undressed, unprotected wounds, and resolved well prior to 90 days, as documented by ultrasounds and histopathology. Conclusions: In vivo and ex vivo models demonstrated thermal values that were below levels known to damage subcutaneous adipose tissue or skin. Tissue histopathology confirmed healing parameters while Doppler ultrasound demonstrated normal blood flow in posttreatment tissues.

Evaluation of the effectiveness of nursing interventions in research from Brazilian postgraduation programs.

PURPOSE: The purpose of this study was to evaluate research from Brazilian postgraduate students who provide evidence of effectiveness for Nursing Interventions Classification (NIC). METHODS: We conducted a literature review study of thesis and dissertations available in the Brazilian Digital Library of Dissertations and Theses (D/T) in May 2021 regardless of the year they were conducted. In those studies that did not utilize the NIC in the effectiveness evaluation, the cross-mapping methodology was employed between NIC and the interventions used by the authors of the studies. RESULTS: Using a systematic process, we identified 91 studies. Twenty-seven met a priori inclusion and exclusion criteria. We found an increase in studies that focused on nursing interventions in the last 10 years (n = 19), a large proportion of clinical trials (n = 16), and the majority of articles from the Southeast region of Brazil (n = 20). The areas of focus were adult and elderly care, and with a special interest in the behavioral domain (n = 11). Two sensitivity criteria were identified in all D/T (n = 27), and each study presented evidence of effectiveness of a minimum of three criteria simultaneously. CONCLUSIONS: Based on the effectiveness criteria, the Brazilian scientific production in postgraduate programs carried out by nurses provides evidence of the effectiveness for NIC nursing interventions. IMPLICATIONS FOR NURSING PRACTICE: It is recommended to conduct further research that uses the NIC in the planning, conduct, and evaluation of interventions, based on effectiveness criteria of nursing sensitivity.

Measurement of femoral and tibial joint reference angles and pelvic limb alignment in cats.

OBJECTIVE: To report pelvic limb joint reference angles, limb alignment, and mechanical axis deviation for the feline pelvic limb. STUDY DESIGN: Cadaveric radiographic anatomic study. ANIMALS: Skeletally mature, mixed breed cats (n = 50). METHODS: Extended pelvic limb radiography was performed and images analyzed to determine femoral anatomic joint reference angles, femoral and tibial mechanical joint reference angles, tibiofemoral angle, metatarsotibial angle, mechanical axis-femur and mechanical axis-metatarsus angles, and mechanical axis deviation of the stifle and tarsus. Mean ± SD and 95% confidence intervals (95% CI) were calculated. RESULTS: Mean ± SD angles and 95% CI were: anatomic lateral proximal femoral (103.9° ± 3.8°; 103.1° - 104.6°), anatomic lateral distal femoral (93.8° ± 2.5°; 93.3° - 94.3°), mechanical lateral proximal femoral (100.5° ± 3.7°; 99.8° - 101.2°), mechanical lateral distal femoral (97.2° ± 2.2°; 96.7° - 97.6°), mechanical medial proximal tibial (88.0° ± 3.2°; 87.3° - 88.6°), mechanical medial distal tibial (107.6° ± 4.8°; 106.6° - 108.5°), mechanical tibiofemoral (7.4° varus ± 2.5°; 6.9° - 7.9°), mechanical metatarsotibial (6.0° valgus ± 3.5°; 5.3° - 6.7°); mechanical axis-femur (3.2° ± 1.4°; 2.9° - 3.5°) and mechanical axis-metatarsus (2.4° ± 2.0°; 1.7° - 2.1°). Mechanical axis deviation of the stifle and of the tarsus were 2.0% ± 0.9% (95% CI: 1.9-2.2) and 0.8% ± 1.0% (95% CI: 0.7-1.0), respectively. CONCLUSIONS: Mean pelvic limb joint reference and limb alignment angles can be used for diagnosing angular limb deformities of the feline pelvic limb and for planning corrective osteotomies in affected cats.

Updates in the Use of Antibiotics, Biofilms.

Guidelines for the rational use of antibiotics are evolving as new understanding of the mechanisms and development of antimicrobial resistance develops. The goals of antibiotic use are to follow the tenets of good antimicrobial stewardship while preventing or treating infection to reduce the risk of developing resistance in bacteria. Biofilm infections also infer microbial resistance and are the cause of recalcitrant infections in humans and animals. Current antibiofilm treatment strategies include the use of antibiotics that can penetrate the biofilm, debridement when possible, dispersal agents, and antibiofilm agents. New and exciting antibiofilm treatment strategies are in various stages of development.

NANDA-I, NOC, and NIC linkages to SARS-CoV-2 (COVID-19): Part 3. Family response.

PURPOSE: To provide guidance to nurses caring for families with COVID-19, we developed linkages using interoperable standardized nursing terminologies: NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). In addition, we wanted to identify gaps in the terminologies and potential new nursing diagnoses, outcomes, and interventions for future development related to nurse roles in family care during a pandemic. METHODS: Using a consensus process, seven nurse experts created the linkages focused on families during the COVID-19 pandemic using the following steps: (1) creating an initial list of potential nursing diagnoses, (2) selecting and categorizing outcomes that aligned with all components of each nursing diagnosis selected, and (3) identifying relevant nursing interventions. FINDINGS: We identified a total of seven NANDA-I nursing diagnoses as the basis for the linkage work. These are distributed in three NANDA-I Domains and based in the psychosocial dimension of the Nursing Care in Response to Pandemics model. Eighty-nine different NOC outcomes were identified to guide care based on the nursing diagnoses, and 54 different NIC interventions were suggested as possible interventions. Fifteen new proposed concepts were identified for future development across the three classifications. CONCLUSIONS: The linkages of nursing diagnoses, outcomes, and interventions provide a guide to enhance nursing practice and care documentation that could quantify the impact of nursing care to patient outcomes for families at risk for or infected by COVID-19. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, NOC, and NIC linkages identified in this paper provide resources to support clinical decisions and guide critical thinking for nurses encountering care needs of families with COVID-19. Documentation of these linkages provides data that can create new knowledge to enhance the care of families impacted by COVID-19.

In vivo analysis in Drosophila reveals differential requirements of contact residues in Axin for interactions with GSK3beta or beta-catenin.

Proper regulation of the Wingless/Wnt signaling pathway is essential for normal development. The scaffolding protein Axin plays a key role in this process through interactions with Drosophila Shaggy and Armadillo. In the current studies, we used a yeast two-hybrid assay to identify ten amino acids in Axin that are critical for in vitro interaction with Shaggy and two for interaction with Armadillo. We then generated five Axin variants in which individual putative contact amino acids were mutated and compared their activity, as assayed by rescue of axin null mutant flies, to that of Axin lacking the entire Shaggy (AxinDeltaSgg) or Armadillo (AxinDeltaArm) binding domain. Although we expected these mutants to function identically to Axin in which the entire binding domain was deleted, we instead observed a spectrum of phenotypic rescue. Specifically, two point mutants within the Shaggy binding domain showed loss of activity similar to that of AxinDeltaSgg and dominantly interfered with complex function, whereas a third mutant allele, AxinK446E, retained most function. Two Axin point mutants within the Armadillo binding domain were weak alleles and retained most function. These findings demonstrate the importance of in vivo verification of the role of specific amino acids within a protein.

Meta-analysis of AKI to CKD transition in perioperative patients.

BACKGROUND: Recent research shows AKI increases the risk of incident CKD. We hypothesized that perioperative AKI may confer increased risk of subsequent CKD compared to nonperioperative AKI. METHODS: A MEDLINE search was performed for "AKI, CKD, chronic renal insufficiency, surgery, and perioperative" and related terms yielded 5209 articles. One thousand sixty-five relevant studies were reviewed. One thousand six were excluded because they were review, animal, or pediatric studies. Fifty-nine studies underwent full manuscript review by two independent evaluators. Seventeen met all inclusion criteria and underwent analysis. Two-by-two tables were constructed from AKI +/- and CKD +/- data. The R package metafor was employed to determine odds ratio (OR), and a random-effects model was used to calculate weighted ORs. Leave-1-out, funnel analysis, and structured analysis were used to estimate effects of study heterogeneity and bias. RESULTS: Nonperioperative studies included studies of oncology, percutaneous coronary intervention, and myocardial infarction patients. Perioperative studies comprised patients from cardiac surgery, vascular surgery, and burns. There was significant heterogeneity, but risk of bias was overall assessed as low. The OR for AKI versus non-AKI patients developing CKD in all studies was 4.31 (95% CI 3.01-6.17; p < 0.01). Nonperioperative subjects demonstrated OR 3.32 for developing CKD compared to non-AKI patients (95% CI 2.06-5.34; p < 0.01) while perioperative patients demonstrated OR 5.20 (95% CI 3.12-8.66; p < 0.01) for the same event. CONCLUSIONS: We conclude that studies conducted in perioperative and nonperioperative patient populations suggest similar risk of development of CKD after AKI.

Autoclaving of Poloxamer 407 hydrogel and its use as a drug delivery vehicle.

With antibiotic-resistant bacteria becoming increasingly prevalent, biomaterials capable of targeted, in situ drug delivery are urgently needed. The synthetic polymer Poloxamer 407 (P407) is of particular interest due to its thermoreversible gelation. Clinical use of P407 typically involves sterilization via autoclaving, but the effects of these extreme environmental conditions on hydrogel water content, rheological properties and efficacy as a drug delivery vehicle remain unknown. The aim of this study was to investigate the effects of autoclaving on the properties of P407 hydrogel. Autoclaving reduced hydrogel water content due to evaporation, thus increasing the polymer weight fraction of the hydrogels. In contrast, except for a reduction in gelation temperature following autoclaving, autoclaved hydrogels had similar rheological properties as nonautoclaved hydrogels. In vitro, autoclaving did not hinder the hydrogel's efficacy as a carrier for vancomycin antibiotic, and P407 (with and without vancomycin) had a bactericidal effect on planktonic Staphylococcus aureus. An in vivo pilot study using P407 to deliver bacteriophage highlighted the need for additional understanding of the functionality of the hydrogel for surgical applications. In conclusion, P407 hydrogel water content and gelation temperature were reduced by autoclave sterilization, while other rheological properties and the efficacy of the biomaterial as a delivery vehicle for vancomycin in vitro were unaffected.

Impact of Deceased Donor Management on Donor Heart Use and Recipient Graft Survival.

BACKGROUND: Current risk-adjusted models used to predict donor heart use and cardiac graft survival from organ donors after brain death (DBDs) do not include bedside critical care data. We sought to identify novel independent predictors of heart use and graft survival to better understand the relationship between donor management and transplantation outcomes. STUDY DESIGN: We conducted a prospective observational study of DBDs managed from 2008 to 2013 by 10 organ procurement organizations. Demographic data, critical care parameters, and treatments were recorded at 3 standardized time points during donor management. The primary outcomes measures were donor heart use and cardiac graft survival. RESULTS: From 3,433 DBDs, 1,134 hearts (33%) were transplanted and 969 cardiac grafts (85%) survived after 684 ± 392 days of follow-up. After multivariable analysis, independent positive predictors of heart use included standard criteria donor status (odds ratio [OR] 3.93), male sex (OR 1.68), ejection fraction > 50% (OR 1.64), and partial pressure of oxygen to fraction of inspired oxygen ratio > 300 (OR 1.31). Independent negative predictors of heart use included donor age (OR 0.94), BMI > 30 kg/m2 (OR 0.78), serum creatinine (OR 0.83), and use of thyroid hormone (OR 0.78). As for graft survival, after controlling for known recipient risk factors, thyroid hormone dose was the only independent predictor (OR 1.04 per µg/h). CONCLUSIONS: Modifiable critical care parameters and treatments predict donor heart use and cardiac graft survival. The discordant relationship between thyroid hormone and donor heart use (negative predictor) vs cardiac graft survival (positive predictor) warrants additional investigation.

Retrospective multicentric study comparing durations of surgery and anesthesia and likelihoods of short- and long-term complications between cats positioned in sternal or dorsal recumbency for perineal urethrostomy.

OBJECTIVE: To compare the durations of surgery and anesthesia and the likelihoods of short- and long-term postoperative complications between cats positioned in sternal recumbency versus dorsal recumbency for perineal urethrostomy (PU). ANIMALS: 247 client-owned cats that underwent PU between January 2004 and December 2015 at 6 veterinary teaching hospitals and 1 private veterinary referral hospital. PROCEDURES: Medical records were reviewed, and signalment, presenting complaints, previous history of urethral obstruction or PU, diet fed, medications administered, indication for PU, durations of surgery and anesthesia for PU, suture type and size, suture pattern for skin closure, and short- and long-term postoperative complications were recorded. Univariable and multivariable analyses were performed to identify differences in durations of surgery and anesthesia and the likelihoods of short- and long-term complications between cats positioned in sternal recumbency and those positioned in dorsal recumbency. RESULTS: Patient position was not associated with durations of surgery and anesthesia for PU, even if a concurrent cystotomy was necessary or the patient required repositioning from sternal to dorsal recumbency. Likewise, patient position was not associated with the likelihood of short- and long-term complications. CONCLUSIONS AND CLINICAL RELEVANCE: The observed lack of differences in outcomes between sternal and dorsal recumbency suggested that logistic considerations and personal preference can continue to guide veterinarians when positioning cats for PU.

Vasopressor selection during critical care management of brain dead organ donors and the effects on kidney graft function.

BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by 17 organ procurement organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, Level III.

Tacrolimus-induced hypomagnesemia and hypercalciuria requires FKBP12 suggesting a role for calcineurin.

Calcineurin inhibitors (CNIs) are immunosuppressive drugs used to prevent graft rejection after organ transplant. Common side effects include renal magnesium wasting and hypomagnesemia, which may contribute to new-onset diabetes mellitus, and hypercalciuria, which may contribute to post-transplant osteoporosis. Previous work suggested that CNIs reduce the abundance of key divalent cation transport proteins, expressed along the distal convoluted tubule, causing renal magnesium and calcium wasting. It has not been clear, however, whether these effects are specific for the distal convoluted tubule, and whether these represent off-target toxic drug effects, or result from inhibition of calcineurin. The CNI tacrolimus can inhibit calcineurin only when it binds with the immunophilin, FKBP12; we previously generated mice in which FKBP12 could be deleted along the nephron, to test whether calcineurin inhibition is involved, these mice are normal at baseline. Here, we confirmed that tacrolimus-treated control mice developed hypomagnesemia and urinary calcium wasting, with decreased protein and mRNA abundance of key magnesium and calcium transport proteins (NCX-1 and Calbindin-D28k ). However, qPCR also showed decreased mRNA expression of NCX-1 and Calbindin-D28k , and TRPM6. In contrast, KS-FKBP12-/- mice treated with tacrolimus were completely protected from these effects. These results indicate that tacrolimus affects calcium and magnesium transport along the distal convoluted tubule and strongly suggests that inhibition of the phosphatase, calcineurin, is directly involved.

Efficacy of a video during bed bath simulation on improving the performance of psychomotor skills of nursing undergraduates: A randomized clinical trial.

BACKGROUND: Studies have shown the efficacy of videos used in isolation to retain knowledge, acquire skills, and establish students' self-confidence. A few studies have investigated the efficacy of videos associated with simulations, while none of these studies have addressed bed bathing, one of the first procedures learned by nursing students. OBJECTIVE: To test the efficacy of a video-assisted bed bath simulation on improving the performance of psychomotor skills of undergraduate nursing students. DESIGN: A randomized clinical trial. SETTING: A Teaching Skills and Simulation Center at a Federal University in Brazil. PARTICIPANTS: All students regularly enrolled in the second year of the nursing undergraduate program at a Federal University, aged 18 years old, who had never performed a bed bath and had attended a theoretical class addressing the procedure (n = 56). METHODS: The students were randomized into two groups: the Control group (n = 28) simulated a bed bath with the instructions of a tutor, while the Intervention group (n = 28) watched a video during the bed bathing simulation, under the supervision of a tutor. The performance of students concerning bed bathing was assessed twice (before and after the simulation) using a previously validated instrument. RESULTS: The psychomotor skills of both groups significantly improved in the second assessment, and the Intervention group scored higher (p = 0.003). CONCLUSIONS: The use of a video during bed bath simulations was efficacious for improving the performance of psychomotor skills of undergraduate nursing students.

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection.

Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.